Synthesis And Bioactivities Of New Polysubstituted2(5H)-Furan-2-one Derivatives

2(5H)-furan-2-one which is also known as γ-butenolide, exist widely innatural products, and is also the important intermediates in the synthesis of naturalproducts. Most of these compounds show great biological activities. They have greatprospects for the development and application in medicine and pesticide and so on.Based on the above findings and our previous works about2(5H)-furan-2-one,two parts research were carried out in this thesis. Firstly, a novel method forpreparing δ-sultone was developed, by which a series of δ-sultones I containing2(5H)-furan-2-one compound were synthesized. And their anti-BVDV activities wereinvestigated and reported for the first time. Secondly, based on the natural bioactivemolecule Uncinine, a series of novel analogues II were designed and synthesized,which showed good tumor cell proliferation inhibitory activity. The main research isas follows:1.Research on the δ-sultone I containing2(5H)-furan-2-oneA novel CSIC reaction for synthesis of the δ-sultone was developed frommesylate I-5which was obtained with phenyl acetic acid as raw material by theesterification reaction, Dieckmann condensation reaction, the hydroxy-protectingreaction and aldol condensation reaction. For the first time the CSIC reaction wasreported with the nucleophilic bases NaOH.By the above method,11target compounds were synthesized whose structureswere characterized by spectra analysis such as NMR, HRMS, IR and X-raydiffraction analysis. They were reported for the first time. Their anti–bovine viraldiarrhea virus (BVDV) activities were evaluated by MTT assay. Most of themshowed excellent anti-viral activity with EC50of0.12μM~1.2μM and low cytotoxicity with CC50of greater than20μM. Among them the ortho bromine phenylderivatives I-6f showed the best antiviral activity with EC50=0.12μM, which was10fold more that of than positive control ribavirin (EC50=1.3μM). BVDV is alsoconsidered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drugstudies. The above results provided a novel candidate for the development ofanti-HCV agents.2. Research on the analogs of Uncinine IIA series of Uncinine analogs were prepared via a facile method with3-methylene-5-butyrolactone as the starting material and3-bromo-methyl-2(5H)-furan-2–one as an important intermediate.24Uncinine analogues were synthesizedby the above method. Their structures have been characterized by spectral analysissuch as IR, NMR and so on. Their anti tumor activities in vitro were tested. Most ofthem showed good anti-tumor activity. Among them, compound II-2a-13showedcomparable anti-tumor activity with IC50=3.764±2.752μM against EC109toUncinine.And compound II-2a-13caused a significant induction of apoptotic cells.In summary,35novel2(5H)-furan-2-ones were prepared. Among them,amount of δ-sultone I containing2(5H)-furan-2-one is11, which showedexcellent antirival activity against BVDV with no significant cytotoxicity. They maybe useful as therapy for the treatment of HCV infection. Amount of Uncicine analogsis24, which showed good anti-tumor activity. The above results are benefit for thedevelopment of new antitumor candidate drug.